Background: Stomach adenocarcinoma (STAD) is a major type of gastric cancer with high morbidity and mortality. , a candidate cancer suppressor gene, has been shown to have anti-cancer effects in various types of cancers. Therefore, comprehensive analyses of in STAD may provide a potential prognostic marker and clinical target for the management of gastric cancer.

Methods: Genomic expression and methylation were analysed based on data from the Human Protein Atlas, Gene Expression Omnibus and Oncomine database. Survival analyses were conducted with the Kaplan-Meier method, using data from The Cancer Genome Atlas database. Immune correlation analyses and prediction of response to immunotherapy were performed using the online Immune Cell Abundance Identifier. Co-expression analyses, functional clustering analyses and construction of a prognostic risk model were conducted in R, with the clinical covariates balanced by the inverse probability treatment weighting method.

Results: was abnormally downregulated in STAD (P<0.05). Survival analysis highlighted a positive association between the expression of and clinical outcomes for patients (P<0.05). Based on co-expression analyses, we found that may be involved in epithelial-mesenchymal transition, gastric cancer stem cells, and responsiveness to chemotherapeutic agents in STAD (P<0.05). Furthermore, functional clustering analysis revealed that was involved in the mTOR signalling pathway, autophagy, and the amino acid starvation response (adjust P<0.05). In addition, was negatively associated with tumour-infiltrating immune cells while positively associated with immunotherapeutic biomarkers in STAD (P<0.05). Meanwhile, patients with high expression were predicted to have a better response to immunotherapy (P<0.05). Finally, a prognostic model constructed based on -related genes could predict the prognosis of STAD patients (AUC =0.641), and the risk score was an independent prognostic factor for STAD patients (HR =4.855, 95% CI: 2.683-8.785, P<0.001).

Conclusions: The present study provided a comprehensive analysis of the role and potential mechanisms of NPRL2 in STAD, suggesting that NPRL2 is a potential biomarker for the survival and prediction of immunotherapy response in STAD.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9459220PMC
http://dx.doi.org/10.21037/jgo-22-115DOI Listing

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